Overview

What are congenital myasthenic syndromes (CMS)?

CMS results from genetic flaws at the neuromuscular junction — where the nerve cell meets the muscle cell.

The type of CMS depends on where the defective gene lies: (A) in the nerve cell — presynaptic CMS; (B) the muscle cell — postsynaptic CMS; or (C) the space in between — synaptic CMS.

Like myasthenia gravis (MG)[1], CMS is characterized by weakness and fatigue resulting from problems at the neuromuscular junction — the place where nerve and muscle cells meet (see illustration at right). But while MG is autoimmune, CMS is an inherited disease caused by defective genes.

There are many types of CMS[2], grouped into three main categories named for the part of the neuromuscular junction that’s affected: presynaptic (the nerve cell), postsynaptic (the muscle cell) or synaptic (the space in between).

What are the symptoms of CMS?

Depending on the type, symptoms of CMS[3] vary from mild to severe, but generally include weakness, fatigue and ptosis (droopy eyelids). The earlier the onset of CMS, the more severe the symptoms are likely to be.

What causes CMS?

With the exception of slow-channel CMS[4], the inheritance pattern for the types of CMS described here is autosomal recessive. This means that it takes two copies of the defective gene — one from each parent — to cause the disease.

Slow-channel CMS is inherited in an autosomal dominant manner. This means that one copy of a defective gene is enough to cause the disease, so an affected parent has a 50 percent chance of passing the disease on to a child.

What is the progression of CMS?

As its name implies, CMS usually has a congenital (at or near birth) onset, but it can manifest in children and even in adults. Later-onset cases tend to be milder.

What is the status of research on CMS?

By identifying the genetic defects that cause CMS, MDA-funded scientists have improved the diagnosis of CMS and discovered drugs that are effective against it. They’re pursuing better drug treatments, and eyeing techniques to fix or replace the underlying genetic defects by gene therapy. For more, see Research[6].